Department of Clinical and Experimental Medicine, Federico II University Medical School of Naples, Via Sergio Pansini 580131 Naples, Italy.
World J Gastroenterol. 2011 Sep 7;17(33):3785-94. doi: 10.3748/wjg.v17.i33.3785.
The incidence of obesity has dramatically increased in recent years. Consequently, obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem. Therefore, the contribution of adipose tissue to metabolic homeostasis has become a focus of interest. In this review, we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease. We describe the common mechanisms (c-Jun amino-terminal kinases, endoplasmic reticulum stress, unfolded protein response, ceramide, low-grade chronic inflammation) by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall. Presenting the molecular mechanism of lipid activation of pro-inflammatory pathways, we attempt to find a link between nonalcoholic fatty liver disease, metabolic syndrome and cardiovascular diseases. Describing the common mechanisms by which lipid derivatives, through modulation of macrophage function, promote plaque instability in the arterial wall, impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of pro-inflammatory pathways, the key roles played by the proliferator-activated receptor and liver X receptor α, nuclear receptors-lipid sensors that link lipid metabolism and inflammation, should be emphasized. Further studies are warranted of anti-inflammatory drugs such as aspirin, anti-interleukin-6 receptors, immune-modulators (calcineurin inhibitors), substances enhancing the expression of heat shock proteins (which protect cells from endoplasmic reticulum stress-induced apoptosis), and anti- c-Jun amino-terminal kinases in well-designed trials to try to minimize the high impact of these illnesses, and the different expressions of the diseases, on the whole population.
近年来，肥胖的发病率显著增加。因此，肥胖症和与之相关的疾病，如非酒精性脂肪肝疾病，构成了一个严重的问题。因此，脂肪组织对代谢稳态的贡献已成为研究的重点。在这篇综述中，我们讨论了支持脂质在非酒精性脂肪肝疾病中作用的最新发现。我们描述了常见的机制（c-Jun 氨基末端激酶、内质网应激、未折叠蛋白反应、神经酰胺、低度慢性炎症），通过这些机制，脂质及其衍生物会损害胰岛素的反应性，并导致肝炎症和促进动脉壁斑块不稳定。提出脂质激活促炎途径的分子机制，我们试图在非酒精性脂肪肝疾病、代谢综合征和心血管疾病之间找到联系。描述脂质衍生物通过调节巨噬细胞功能促进动脉壁斑块不稳定、损害胰岛素反应性并导致肝炎症的共同机制，并讨论脂质激活促炎途径的分子机制，强调了核受体-脂质传感器在连接脂质代谢和炎症中的关键作用，这些核受体包括增殖激活受体和肝 X 受体 α。有必要进一步研究抗炎药物，如阿司匹林、抗白细胞介素 6 受体、免疫调节剂（钙调神经磷酸酶抑制剂）、增强热休克蛋白表达的物质（保护细胞免受内质网应激诱导的细胞凋亡）和抗 c-Jun 氨基末端激酶，以进行精心设计的试验，试图最大限度地减少这些疾病以及这些疾病在整个人群中的不同表现对人们健康的高影响。
